Pharmacological profile of essential oils derived from Lavandula angustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels.
Both Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils have putative anti-agitation properties in humans, indicating common components with a depressant action in the central nervous system. A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically validated essential oil derived from La, which has shown clinical benefit in treating agitation. La inhibited [35S] TBPS binding to the rat forebrain gamma aminobutyric acid (GABA)(A) receptor channel (apparent IC50 = 0.040 +/- 0.001 mg mL(-1)), but had no effect on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or nicotinic acetylcholine receptors. A 50:50 mixture of Mo and La essential oils inhibited [3H] flunitrazepam binding, whereas the individual oils had no significant effect. Electrophysiological analyses with rat cortical primary cultures demonstrated that La reversibly inhibited GABA-induced currents in a concentration-dependent manner (0.01-1 mg mL(-1)), whereas no inhibition of NMDA- or AMPA-induced currents was noted. La elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission, with a net depressant effect on neurotransmission (in contrast to the classic GABA(A) antagonist picrotoxin which evoked profound epileptiform burst firing in these cells). These properties are similar to those recently reported for Mo. The anti-agitation effects in patients and the depressant effects of La we report in neural membranes in-vitro are unlikely to reflect a sedative interaction with any of the ionotropic receptors examined here. These data suggest that components common to the two oils are worthy of focus to identify the actives underlying the neuronal depressant and anti-agitation activities reported.
Huang
Liping
L
Department of Pharmacology & Toxicology, University of Otago, PO Box 913, Dunedin, New Zealand.
Abuhamdah
Sawsan
S
Howes
Melanie-Jayne R
MJ
Dixon
Christine L
CL
Elliot
Mark S J
MS
Ballard
Clive
C
Holmes
Clive
C
Burns
Alistair
A
Perry
Elaine K
EK
Francis
Paul T
PT
Lees
George
G
Chazot
Paul L
PL
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020128:Inhibitory Concentration 50; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D027523:Lavandula / Q000737:chemistry*; D008024:Ligands; D008297:Male; D031334:Melissa / Q000737:chemistry*; D009822:Oils, Volatile / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D011595:Psychomotor Agitation / Q000188:drug therapy; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism
D007473:Ion Channels; D008024:Ligands; D009822:Oils, Volatile; D011963:Receptors, GABA-A